BRG1-SWI/SNF-dependent regulation of the Wt1 transcriptional landscape mediates epicardial activity during heart development and disease

• DOI: 10.1038/ncomms16034
• Publication Date: 2017-07-24T10:20:46Z
• Authors: Joaquim Miguel Vi...; Sara Howard; Cristina Villa de...; Sveva Bollini; Karina N. Dubé; Megan Masters; Damien N. Barnette; Mala Rohling; Xin Sun; Laura E. Hankins; Daria Gavriouchkina; Ruth Williams; Daniel Metzger; Pierre Chambon; Tatjana Sauka-Spe...; Benjamin Davies; Paul R. Riley
• Keywords: SWI/SNF; Chromatin immunoprecipitation; Heart development

Epicardium-derived cells (EPDCs) contribute cardiovascular cell types during development and in adulthood respond to Thymosin β4 (Tβ4) myocardial infarction (MI) by reactivating a fetal gene programme promote neovascularization cardiomyogenesis. The mechanism for epicardial (re-)activation remains elusive. Here we reveal that BRG1, the essential ATPase subunit of SWI/SNF chromatin-remodelling complex, is required expression Wilms' tumour 1 (Wt1), EPDC activation subsequent differentiation into coronary smooth muscle, restores Wt1 activity upon MI. BRG1 physically interacts with Tβ4 recruited CCAAT/enhancer-binding protein β (C/EBPβ) discrete regulatory elements locus. BRG1-Tβ4 co-operative binding promotes optimal transcription as master regulator embryonic EPDCs. Moreover, chromatin immunoprecipitation-sequencing reveals at further key loci suggesting across programme. These findings functions EPDCs repair.